The current contract has been issued to extend and complete the findings of the previous contract N01-HD-6-2926 on which Dr. Bernfield was the offeror. Under the previous contract Dr. Bernfield had developed a model for spina bifida, the curly tail mouse and had shown that the defect in neural tube closure could be correlated with a reduction in hyaluronic acid in the region of the closing neural folds. Further, he and his colleagues had shown that there appeared to be imbalance between the growth rates of the neural ectoderm and the underlying tissues in embryos destined to produce spina bifida. Under this contract, the Offeror and his collaborators will examine the changes in hyaluronic acid homeostasis at the molecular level employing specific probes to quantify synthesis and degradation of the glycoprotein. They will also address the role of differences in growth rates in the production of neural tube defects by crossing strains of mice shown to differ in their growth rates. These recombinant mice will be examined for the relationship between the genetically regulated rate of development and the potential for producing unbalanced growth processes in the posterior neuropore region. If these studies are successful they will point to gene loci which are important in controlling the rate of growth and provide a basis for the multifactorial genetic mechanisms hypothesized to cause neura tube defects.